The Effect of Umbilical Cord Blood Derived Mesenchymal Stem Cells in Monocrotaline-induced Pulmonary Artery Hypertension Rats.
10.3346/jkms.2015.30.5.576
- Author:
Hyeryon LEE
1
;
Jae Chul LEE
;
Jung Hyun KWON
;
Kwan Chang KIM
;
Min Sun CHO
;
Yoon Sun YANG
;
Wonil OH
;
Soo Jin CHOI
;
Eun Seok SEO
;
Sang Joon LEE
;
Tae Jun WANG
;
Young Mi HONG
Author Information
1. Department of Pediatrics, Ewha Womans University School of Medicine, Seoul, Korea. ymhong@ewha.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Hypertension;
Pulmonary;
Monocrotaline;
Cord Blood Stem Cell Transfusion;
Gene Expression
- MeSH:
Animals;
Cytokines/metabolism;
Disease Models, Animal;
Endothelin-1/metabolism;
Fetal Blood/*cytology;
Gene Expression Regulation/drug effects;
Hemodynamics;
Humans;
Hypertension, Pulmonary/chemically induced/*therapy;
Hypertrophy, Right Ventricular/physiopathology;
Immunohistochemistry;
Lung/metabolism/pathology;
Male;
Matrix Metalloproteinase 2/metabolism;
*Mesenchymal Stem Cell Transplantation;
Mesenchymal Stromal Cells/*cytology/metabolism;
Monocrotaline/toxicity;
Nitric Oxide Synthase Type III/metabolism;
Pulmonary Artery/pathology;
Rats;
Rats, Sprague-Dawley;
Receptor, Endothelin A/metabolism
- From:Journal of Korean Medical Science
2015;30(5):576-585
- CountryRepublic of Korea
- Language:English
-
Abstract:
Pulmonary arterial hypertension (PAH) causes right ventricular failure due to a gradual increase in pulmonary vascular resistance. The purposes of this study were to confirm the engraftment of human umbilical cord blood-mesenchymal stem cells (hUCB-MSCs) placed in the correct place in the lung and research on changes of hemodynamics, pulmonary pathology, immunomodulation and several gene expressions in monocrotaline (MCT)-induced PAH rat models after hUCB-MSCs transfusion. The rats were grouped as follows: the control (C) group; the M group (MCT 60 mg/kg); the U group (hUCB-MSCs transfusion). They received transfusions via the external jugular vein a week after MCT injection. The mean right ventricular pressure (RVP) was significantly reduced in the U group after the 2 week. The indicators of RV hypertrophy were significantly reduced in the U group at week 4. Reduced medial wall thickness in the pulmonary arteriole was noted in the U group at week 4. Reduced number of intra-acinar muscular pulmonary arteries was observed in the U group after 2 week. Protein expressions such as endothelin (ET)-1, endothelin receptor A (ERA), endothelial nitric oxide synthase (eNOS) and matrix metalloproteinase (MMP)-2 significantly decreased at week 4. The decreased levels of ERA, eNOS and MMP-2 immunoreactivity were noted by immnohistochemical staining. After hUCB-MSCs were administered, there were the improvement of RVH and mean RVP. Reductions in several protein expressions and immunomodulation were also detected. It is suggested that hUCB-MSCs may be a promising therapeutic option for PAH.
